Depletion of natural CD4( )CD25( ) T regulatory cells with anti-CD25 antibody does not change the course of Pseudomonas aeruginosa-induced acute lung infection in mice

作者：Carrigan Svetlana O; Yang Yong Jun; Issekutz Thomas; Forward Nicholas; Hoskin David; Johnston Brent; Lin Tong Jun^*

来源：Immunobiology, 2009, 214(3): 211-222.

DOI：10.1016/j.imbio.2008.07.027

• Inflammation
• Innate immunity
• Lung infection
• Pseudomonas aeruginosa
• Regulatory T cells

Pseudomonas aeruginosa is a common cause of lung infection in immune compromised individuals. Studies in humans and mice have demonstrated that P. aeruginosa lung infection is associated with a predominant Th2 immune response, whereas Th1 responses are accompanied by a better pulmonary outcome. Regulatory T cells (Tregs) are a subpopulation of T cells with unique immunologic characteristics that suppress effector T cell functions. Whether Tregs contribute to P. aeruginosa-induced host responses has not been studied previously. We found that P. aeruginosa lung infection induced an increase in natural Treg cells (CD4(+)CD25(+)FOXP3(+) T cells) in the spleen of mice. To investigate a role of natural CD4(+)CD25(+) Tregs in the host response to P. aeruginosa lung infection in vivo, anti-CD25 Ab was used to deplete endogenous CD4(+)CD25(+) Tregs. Anti-CD25 treatment depleted 90% of CD4(+)CD25(+) FOXP3(+) cells. Surprisingly, no differences of P. aeruginosa-induced NF-kappa B activation and cytokine/chemokine production (IL-1 beta, TNF, IL-6, IL-10, RANTES or MIP-2) were observed between anti-CD25-treated and isotype control Ab-treated animals. Similarly, no differences in lung histology and airway neutrophil infiltration were observed between anti-CD25 and control Ab-treated animals. Furthermore, no difference in survival outcome was found between anti-CD25 and control Ab-treated animals. These data demonstrate that although P. aeruginosa lung infection causes an increase of Tregs, the endogenous natural CD4(+)CD25(+) Treg cells do not contribute significantly to the host response to this bacterium.

• 出版日期2009-3